Personalized dosing of cyclophosphamide in the total body irradiation-cyclophosphamide conditioning regimen: a phase II trial in patients with hematologic malignancy.
Clin Pharmacol Ther
; 85(6): 615-22, 2009 Jun.
Article
em En
| MEDLINE
| ID: mdl-19295506
ABSTRACT
This study investigates the efficacy and safety of personalized cyclophosphamide (CY) dosing in 50 patients receiving CY along with total body irradiation (TBI). Participants received CY 45 mg/kg with subsequent therapeutic drug monitoring using Bayesian parameter estimation to personalize the second CY dose to a target area under the curve (AUC) for carboxyethylphosphoramide mustard (CEPM) (a reporter molecule for CY-derived toxins) and for hydroxycyclophosphamide (to ensure engraftment). The mean second CY dose was 66 mg/kg; the total dose ranged from 45 to 145 mg/kg. After completion of this phase II study, we compared participants' clinical outcomes with those of concurrent controls (n = 100) who received TBI along with standard CY doses of 120 mg/kg. Patients receiving personalized CY dosing had significantly lower postconditioning peak total serum bilirubin (P = 0.03); a 38% reduction in the hazard of acute kidney injury (AKI) (P = 0.03); and nonrelapse and overall survival rates similar to those in the controls (P = 0.70 and 0.63, respectively) despite the lower doses of CY administered to most of the patients in the personalized dosage group.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transplante de Células-Tronco Hematopoéticas
/
Antineoplásicos Alquilantes
/
Neoplasias Hematológicas
/
Condicionamento Pré-Transplante
/
Ciclofosfamida
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article